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International

                                                                         Journal of Bioprinting



                                        RESEARCH ARTICLE
                                        Development and applications of an in vitro

                                        non-alcoholic fatty liver disease model based on
                                        3D-printed liver tissue



                                        Kun Du 1 id , Wei Peng 2 id , Ying Zhao 2 id , Tianma He 2 id , Tao Ding 2 id , Feifei Pu 3 id ,
                                        Zibei Ming 2 id , Renquan Ruan 4 id , and Jing Liu *
                                                                              2 id
                                        1  Department of Medical Equipment, Wuhan No. 1 Hospital, Wuhan, Hubei, China
                                        2  Department of Biological Engineering, School of Biology, Food and Environment, Hefei University,
                                        Hefei, Anhui, China
                                        3  Department of Orthopedics, Wuhan No.1 Hospital, Wuhan, Hubei, China
                                        4  Shenzhen Mellgen Biotechnology Co. Ltd., Shenzhen, Guangdong, China




                                        Abstract

                                        Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic disease worldwide,
                                        but its underlying etiology and molecular mechanisms are complex, and there
                                        are  currently  no  effective  clinical  treatments.  Animal  models  for  studying  NAFLD
                                        have limitations, necessitating the development of novel  in vitro models. In this
                                        study, a bioink was first optimized for the cultivation of liver tissue. Subsequently,
                                        3D bioprinting technology was utilized to construct large-scale liver tissue with a
                                        vascular-like function  in vitro using the optimized bioink. Thereafter, the printed
            *Corresponding author:      HepaRG cells were induced to form liver organoids. Compared with traditional liver
            Jing Liu (liujing@hfuu.edu.cn)  tissue  models,  3D-printed  liver  tissue  has  superior  hepatic  functions  and  greater
            Citation: Du K, Peng W, Zhao Y,    cell viability. Moreover, glycogen storage and the formation of bile canaliculi-like
            et al. Development and applications   structures were observed within it. Subsequently, 3D-printed liver tissue was induced
            of an in vitro non-alcoholic fatty    to establish an NAFLD model, which was confirmed by lipid droplet analysis, liver
            liver disease model based on
            3D-printed liver tissue.    function assays, and cell viability assessments. Additionally, this NAFLD model was
            Int J Bioprint. 2024;10(6):4312.    used for drug testing and analysis. Our study successfully constructed a functional
            doi: 10.36922/ijb.4312      NAFLD model, which contributes to a deeper understanding of the mechanisms
            Received: July 23, 2024     underlying  NAFLD,  facilitates  the  development  of related  pharmaceuticals,  and
            Revised: September 2, 2024  promotes the development of new therapeutic strategies.
            Accepted: September 18, 2024
            Published Online: September 18,
            2024
                                        Keywords: Non-alcoholic fatty liver disease; 3D bioprinting; Large-scale liver tissue;
            Copyright: © 2024 Author(s).   In vitro model; Drug testing
            This is an Open Access article
            distributed under the terms of the
            Creative Commons Attribution
            License, permitting distribution,
            and reproduction in any medium,   1. Introduction
            provided the original work is
            properly cited.             Non-alcoholic fatty liver disease (NAFLD) is currently one of the most prevalent
            Publisher’s Note: AccScience   chronic diseases worldwide and is significantly associated with obesity and metabolic
            Publishing remains neutral with   disorders. The global prevalence of NAFLD is estimated to be approximately 25% of the
            regard to jurisdictional claims in                                      1
            published maps and institutional   population, with an increasing trend observed annually.  Early-stage NAFLD is generally
            affiliations.               asymptomatic and does not affect patient survival; however, if left untreated, it can




            Volume 10 Issue 6 (2024)                       360                                doi: 10.36922/ijb.4312
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